中性粒细胞在血液的非特异性细胞免疫系统中起着十分重要的作用，它处于机体抵御微生物病原体入侵的第一线，特别是对于化脓性细菌而言。中性粒细胞是参与组织炎症反应的第一种免疫细胞，在炎症部位发出信号，吸引大量白细胞聚集至炎症部位。2型糖尿病患者中多数存在胰岛素抵抗现象。有研究表明，在脂肪组织中常见的慢性低度炎症是系统性胰岛素抵抗的重要诱因。近日，圣地亚哥加利福尼亚大学医学系的研究人员针对中性粒细胞介导胰岛素抵抗进行了相关研究。

　　研究人员首先用高脂肪饮食喂养小鼠诱导肥胖小鼠模型，并敲除小鼠嗜中性粒细胞弹性蛋白酶（neutrophilelastase,NE）基因，结果导致组织炎症减少，这还与脂肪组织中嗜中性粒细胞和巨噬细胞水平的降低有关。这些转变还伴随着葡萄糖耐受性的增高，并增加了胰岛素的敏感性。研究人员将上述观察到的现象综合在一起发现，中性粒细胞所分泌的NE影响了胰岛素信号通路，激发了胰岛素抵抗。嗜中性粒细胞利用NE来激活一种触发吞噬病原体的巨噬细胞分泌促炎症分子(proinflammatorymolecule)的信号通路。NE能够降解一种在肝细胞和脂肪细胞胰岛素信号通路中发挥关键性作用的蛋白——胰岛素受体底物1(insulinreceptorsubstrate1，IRS1)。

　　该试验显示，NE对肝脏和脂肪组织的胰岛素靶组织的影响是十分显著的。嗜中性粒细胞调节胰岛素的作用使得它们成为一种新的靶标，从而能够被用来开发。

　　Chronic low-grade adipose tissue and liver inflammation is a major cause of systemic insulin resistance and is a key component of the low degree of insulin sensitivity that exists in obesity and type 2 diabetes1, 2. Immune cells, such as macrophages, T cells, B cells, mast cells and eosinophils, have all been implicated as having a role in this process3, 4, 5, 6, 7, 8. Neutrophils are typically the first immune cells to respond to inflammation and can exacerbate the chronic inflammatory state by helping to recruit macrophages and by interacting with antigen-presenting cells9, 10, 11. Neutrophils secrete several proteases, one of which is neutrophil elastase, which can promote inflammatory responses in several disease models12. Here we show that treatment of hepatocytes with neutrophil elastase causes cellular insulin resistance and that deletion of neutrophil elastase in high-fat-diet–induced obese (DIO) mice leads to less tissue inflammation that is associated with lower adipose tissue neutrophil and macrophage content. These changes are accompanied by improved glucose tolerance and increased insulin sensitivity. Taken together, we show that neutrophils can be added to the extensive repertoire of immune cells that participate in inflammation-induced metabolic disease.